The following discussion of the background of the invention is provided to aid the reader in understanding the invention and is not an admission that anything herein describes or constitutes prior art.
Systemic iron homeostasis is dependent on the expression of the liver peptide hormone hepcidin and its interaction with the cell surface iron transporter ferroportin (Fpn) (for review see (1)). Fpn exports iron from cells to the plasma and is responsible for iron absorption from the intestine, recycling of erythrocyte iron by macrophages and maternal delivery of iron to the fetus. Transcription of hepcidin in hepatocytes is regulated by the levels of cytokines, hypoxia and iron stores. Once secreted, hepcidin binds to Fpn and induces its internalization and degradation (2). Binding of hepcidin to Fpn leads to the phosphorylation of either of two adjacent tyrosines in a cytosolic domain resulting in the internalization of phosphorylated Fpn by coated pits (3). Mutations in Fpn that prevent hepcidin binding to Fpn or Fpn phosphorylation subsequent to hepcidin binding, and Fpn/hepcidin internalization, result in hepatic iron overload disease (4). The low level of hepcidin in plasma and the lack of useful anti-hepcidin antibodies have made assay of plasma hepcidin levels problematic, although it may be assayable by mass spectroscopy.
Hepcidin deficiency or alterations in ferroportin result in dysregulated iron absorption, tissue maldistribution of iron, and iron overload. For example, hepcidin deficiency has been reported in hereditary hemochromatosis and is attributed to mutations in HFE, transferrin receptor 2, hemojuvelin, and the hepcidin gene itself. Hepcidin levels have been found to be suppressed in patients with thalassemia syndromes, congenital dyserythropoietic anemia type 1, juvenile hemochromatosis, and hereditary hemochromatosis (type 1 hemochromatosis). Hepcidin levels have also been found to be elevated in patients with hemochromatosis type 4 (ferroportin disease) and anemia of inflammation. As a result of hepcidin's critical role in iron homeostasis, measurement of hepcidin levels is important in the diagnosis and treatment of iron homeostasis diseases and disorders.
Hence, there is a need in the art for a reliable and rapid diagnostic, prognostic and/or predictive method that can accurately measure hepcidin levels in a biological fluid.